The continuing development of synthesis strategies based on the chemistry of alkynyliodonium salts and their derived alkylidenecarbenes will occupy the majority of the proposed efforts. The alkynyliodonium salt-based chemistry will find purchase in total synthesis efforts directed toward members of the kinamycin family of antibiotics such kinamycin F, as well as designed analogues that will be used to probe a novel mechanism-of-action hypothesis distinct from those found in the literature. Insight into the mechanism-of-action of these potent anticancer agents can further the design and development of novel small-molecule cancer chemotherapeutics. In addition, use of alkynyliodonium salt chemistry to gain access to belted dihydropyrroles en route to a unified strategy for the enantioselective syntheses of the macrocyclic prodigiosins metacycloprodigiosin and streptorubin B will showcase the value of linking hypervalent iodine chemistry with downstream olefin metathesis transformations for the efficient synthesis of highly functionalized pyrroles. Successful execution of this work will lead to assignment of the absolute stereochemistry of both species, and, surprisingly, the (currently unknown) relative stereochemistry of streptorubin B. The complete stereochemical definition of these promising immunosuppressive compounds will serve as a foundation for mechanism-of-action and structure-activity studies directed toward developing new transplant-rejection therapies that feature minimal cytotoxicity.